Abstract
Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of parasite antigen-specific regulatory T cells. Here we addressed whether such early-onset cellular immunological alterations persist through infancy. Specifically, in order to assess the potential impacts of P. falciparum infections either during pregnancy or during infancy, we quantified lymphocyte subsets in cord blood and in infants' peripheral blood during the first year of life. The principal age-related changes observed, independent of infection status, concerned decreases in the frequencies of CD4+, NKdim and NKT cells, whilst CD8+, Treg and Teff cells' frequencies increased from birth to 12 months of age. P. falciparum infections present at delivery, but not those earlier in gestation, were associated with increased frequencies of Treg and CD8+ T cells but fewer CD4+ and NKT cells during infancy, thus accentuating the observed age-related patterns. Overall, P. falciparum infections arising during infancy were associated with a reversal of the trends associated with maternal infection i.e. with more CD4+ cells, with fewer Treg and CD8+ cells. We conclude that maternal P. falciparum infection at delivery has significant and, in some cases, year-long effects on the composition of infants' peripheral blood lymphocyte populations. Those effects are superimposed on separate and independent age- as well as infant infection-related alterations that, respectively, either match or run counter to them.
Highlights
Infectious diseases during pregnancy affect infants’ responses to vaccination [1, 2] their susceptibility to postnatal infection [3] and their development of immunopathological disorders such as allergy [4]
Data were adjusted on the P. falciparum infection history of the mother, gravidity, infant age, low birth weight. *Results cumulate both NKdim and NKbright to avoid introducing two variables that are highly correlated into the model
The characterization of factors associated with increased susceptibility of infants to P. falciparum infection during the first year of life is a priority in the development of a vaccine against malaria
Summary
Infectious diseases during pregnancy affect infants’ responses to vaccination [1, 2] their susceptibility to postnatal infection [3] and their development of immunopathological disorders such as allergy [4]. These detrimental and long-lasting outcomes are the result of exposures in utero that alter foetal immune responses. Examples of diseases known to have such effects include the malaria parasite, Plasmodium falciparum, Trypanosoma cruzi, the cause of Chagas’ disease, Schistosoma spp that cause bilharzia, and Wuchereria bancrofti, one of the species of nematode worm responsible for filariasis [5,6,7,8]. PAM leads to a higher risk of maternal and foetal anemia, intra-uterine growth retardation, low birth weight and prematurity [10]
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